The peroxynitrite catalyst WW-85 improves microcirculation in ovine smoke inhalation injury and septic shock

Dirk M. Maybauer, Marc O. Maybauer, Csaba Szabó, Martin Westphal, Lillian D. Traber, Andrew L. Salzman, David N. Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

This prospective, randomized, controlled experimental study examined the effects of the peroxynitrite decomposition catalyst WW-85 on global hemodynamics and regional microvascular blood flow (RMBF) in an established ovine model of septic shock following severe smoke inhalation injury. Twenty-one sheep were randomized into a sham group (no injury), a control group (smoke/sepsis), and a treatment group (smoke/sepsis/WW-85; n = 7 each). WW-85 was administered 1 h after injury as a bolus (0.1 mg/kg), followed by a continuous infusion of 0.02 mg/kg/h RMBF was analyzed using colored microspheres. All control animals developed a hypotensive, hyperdynamic circulation and increased plasma levels of nitrate/-nitrite (NOx). All hemodynamic variables and NOx levels were significantly improved in the treatment group. In visceral organs of controls, blood flow to trachea, ileum, and spleen significantly increased (p < 0.05). Blood flow to kidneys and pancreas significantly decreased (p < 0.05). Treatment with WW-85 stabilized blood flow to ileum, spleen, and kidneys on baseline levels and was significantly improved compared to controls (p < 0.05). Cerebral blood flow deteriorated in controls, but was significantly improved in cerebral cortex, cerebellum, pons, medulla oblongata, and thalamus (p < 0.05) by WW-85. These results provide evidence that WW-85 blocks NO production, thereby improving cardiovascular function and microcirculation.

Original languageEnglish (US)
Pages (from-to)842-850
Number of pages9
JournalBurns
Volume37
Issue number5
DOIs
StatePublished - Aug 2011

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Keywords

  • ARDS
  • Acute lung injury
  • Cerebral autoregulation
  • Cerebral blood flow
  • Nitric oxide
  • Smoke inhalation

ASJC Scopus subject areas

  • Surgery
  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Maybauer, D. M., Maybauer, M. O., Szabó, C., Westphal, M., Traber, L. D., Salzman, A. L., Herndon, D. N., & Traber, D. L. (2011). The peroxynitrite catalyst WW-85 improves microcirculation in ovine smoke inhalation injury and septic shock. Burns, 37(5), 842-850. https://doi.org/10.1016/j.burns.2010.12.020